rs1048753323
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7
The NM_000156.6(GAMT):c.9C>T(p.Ala3=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000365 in 1,369,164 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)
Exomes 𝑓: 8.2e-7 ( 0 hom. )
Consequence
GAMT
NM_000156.6 synonymous
NM_000156.6 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.736
Genes affected
GAMT (HGNC:4136): (guanidinoacetate N-methyltransferase) The protein encoded by this gene is a methyltransferase that converts guanidoacetate to creatine, using S-adenosylmethionine as the methyl donor. Defects in this gene have been implicated in neurologic syndromes and muscular hypotonia, probably due to creatine deficiency and accumulation of guanidinoacetate in the brain of affected individuals. Two transcript variants encoding different isoforms have been described for this gene. Pseudogenes of this gene are found on chromosomes 2 and 13. [provided by RefSeq, Feb 2012]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -5 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.78).
BP6
?
Variant 19-1401468-G-A is Benign according to our data. Variant chr19-1401468-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 478019.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
Synonymous conserved (PhyloP=0.736 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GAMT | NM_000156.6 | c.9C>T | p.Ala3= | synonymous_variant | 1/6 | ENST00000252288.8 | |
GAMT | NM_138924.3 | c.9C>T | p.Ala3= | synonymous_variant | 1/5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GAMT | ENST00000252288.8 | c.9C>T | p.Ala3= | synonymous_variant | 1/6 | 1 | NM_000156.6 | P1 | |
GAMT | ENST00000447102.8 | c.9C>T | p.Ala3= | synonymous_variant | 1/5 | 2 | |||
GAMT | ENST00000640762.1 | c.9C>T | p.Ala3= | synonymous_variant | 1/6 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.0000263 AC: 4AN: 152008Hom.: 0 Cov.: 32
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GnomAD4 exome AF: 8.22e-7 AC: 1AN: 1217156Hom.: 0 Cov.: 31 AF XY: 0.00000169 AC XY: 1AN XY: 592352
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GnomAD4 genome ? AF: 0.0000263 AC: 4AN: 152008Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74248
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Cerebral creatine deficiency syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jun 25, 2023 | - - |
Computational scores
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BayesDel_noAF
Benign
Cadd
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Dann
Benign
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at